G Protein

Signal Transduction

Trimer protein responsible for amplification/transduction?

Guanine Nucleotide Binding Proteins

Purine

Function/Purpose:

• Molecular switch
  • GTP - ON
  • GDP - OFF
• Inhibition or Stimulation:
  • Ion Channels
  • Membrane Bound Enzymes

Stratification:

• 20 types

Components:

• Alpha subunit (GDP)
• Beta subunit
• Gamma subunit

General Mechanism:

Adrenergic Receptor

• Ligand binds to receptor binds
• Conformation changes throughout the Seven Transmembrane-helix (7TM)receptor

G Protein Coupling

• Gprotein binds to newly changed conformation of 7TM
• Binding to 7TM creates a conformational change (GDP-->GTP) and Gprotein components breaks off
  • Galpha (GTP) breaks off from Gbetagamma and seeks target protein

Target Acquisition

• GTP activates target protein
• Hydrolysis of GTP by the alpha subunit inactivates and causes breaking off from the target protein
• GDP seeks Gbetagamma to remain become inactive

G Protein Analogy: Military

Secondary Messengers:

• cAMP
• IP3
• DAG
• Calcium (Ca)

LOC:

• Intracellular space/Cytosol side of membrane

Similar Mechanisms:

Ras

• Similar to G Proteinalpha that is GDP which becomes GTP through the oxidation of a GTP or creates an exchange of GTP
• Has an intrinsic GTPase activity: slow but augmented by helper proteins - GTPase activating proteins (GAPs)

Small G proteins/small GTPases

Stimulate Cell Growth and Differentiation

• Ras regulates cell growth through SER and THR protein kinases
• Rho reorganizes cytoskeleton through SER and THR protein kinases
• Arf activates ADP-ribosyltransferase of cholera toxin A1 subunit, regulates vesicular trafficking pathways, activates phospholipase D
• Rab key role in secretory and endocytotic pathways
• Ran transport RNA and protein into and out of the nucleus

Diseases:

• Cholera
• Whooping Cough

Additional Information:

• Wikipedia